OAT

ornithine aminotransferase

Basic information

Region (hg38): 10:124397303-124418976

Links

ENSG00000065154 ∙ NCBI:4942 ∙ OMIM:613349 ∙ HGNC:8091 ∙ Uniprot:P04181 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ornithine aminotransferase deficiency (Supportive), mode of inheritance: AR
• ornithine aminotransferase deficiency (Strong), mode of inheritance: AR
• ornithine aminotransferase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gyrate atrophy of choroid and retina	AR	Biochemical	Dietary management (eg, with arginine restriction) may be beneficial	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	4122112; 572946; 7444439; 7356686; 3339136; 1737786; 11831916; 10604138; 110617919; 1297489; 15750329; 22674428; 34340878

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OAT gene.

• Ornithine aminotransferase deficiency (49 variants)
• Hyperornithinemia (3 variants)
• Gyrate atrophy of choroid and retina with pyridoxine-responsive ornithinemia (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OAT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	161	1	163
missense	8	11	127	2		148
nonsense	15	13				28
start loss	3					3
frameshift	18	14				32
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	14				18
splice region	1		10	24	1	36
non coding			16	81	53	150
Total	48	52	145	244	54

Highest pathogenic variant AF is 0.000197

Variants in OAT

This is a list of pathogenic ClinVar variants found in the OAT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-124397381-C-T		Ornithine aminotransferase deficiency	Uncertain significance (Jan 13, 2018)
10-124397407-A-G		Ornithine aminotransferase deficiency	Benign (Jan 13, 2018)
10-124397456-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Jan 13, 2018)
10-124397564-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Jan 13, 2018)
10-124397631-A-G		Ornithine aminotransferase deficiency	Uncertain significance (Jan 12, 2018)
10-124397667-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Jan 12, 2018)
10-124397753-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Jan 13, 2018)
10-124397757-G-A		Ornithine aminotransferase deficiency	Benign (Aug 15, 2018)
10-124397881-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Jan 12, 2018)
10-124397907-G-A		Ornithine aminotransferase deficiency	Uncertain significance (Jan 12, 2018)
10-124397942-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Aug 31, 2021)
10-124397948-A-G		Ornithine aminotransferase deficiency	Likely benign (Aug 05, 2022)
10-124397950-A-T		Ornithine aminotransferase deficiency	Uncertain significance (Feb 02, 2022)
10-124397951-C-A		Ornithine aminotransferase deficiency	Conflicting classifications of pathogenicity (Jan 29, 2024)
10-124397951-C-G		Ornithine aminotransferase deficiency	Benign (Feb 15, 1992)
10-124397951-C-T		Ornithine aminotransferase deficiency	Likely benign (Dec 13, 2023)
10-124397953-A-G		Ornithine aminotransferase deficiency	Likely benign (Nov 14, 2023)
10-124397955-A-T		Ornithine aminotransferase deficiency • Hyperornithinemia	Pathogenic/Likely pathogenic (Feb 27, 2024)
10-124397957-G-A		Ornithine aminotransferase deficiency • OAT-related disorder	Likely benign (Jan 18, 2024)
10-124397957-G-T		Ornithine aminotransferase deficiency	Likely benign (Sep 25, 2023)
10-124397961-T-G		Ornithine aminotransferase deficiency • Inborn genetic diseases	Uncertain significance (Aug 06, 2024)
10-124397962-T-C		Ornithine aminotransferase deficiency	Uncertain significance (Aug 13, 2021)
10-124397963-G-A		Ornithine aminotransferase deficiency	Likely benign (Feb 04, 2022)
10-124397968-T-A		Ornithine aminotransferase deficiency	Uncertain significance (Mar 11, 2022)
10-124397969-A-T		Ornithine aminotransferase deficiency	Likely benign (Dec 04, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OAT	protein_coding	protein_coding	ENST00000368845	9	21674

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.72e-7	0.913	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.876	204	242	0.842	0.0000129	2848
Missense in Polyphen		63	92.108	0.68398		1129
Synonymous	1.01	81	93.4	0.867	0.00000563	882
Loss of Function	1.70	13	21.5	0.605	0.00000121	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000359	0.000358
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000246	0.000246
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Hyperornithinemia with gyrate atrophy of choroid and retina (HOGA) [MIM:258870]: A disorder clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence. {ECO:0000269|PubMed:1612597, ECO:0000269|PubMed:1737786, ECO:0000269|PubMed:23076989, ECO:0000269|PubMed:2793865, ECO:0000269|PubMed:3375240, ECO:0000269|PubMed:7668253, ECO:0000269|PubMed:7887415}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Amino Acid metabolism;Urea cycle and metabolism of amino groups;Metabolism of amino acids and derivatives;Metabolism;ornithine <i>de novo </i> biosynthesis;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Arginine Proline metabolism;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.642

Intolerance Scores

• loftool: 0.0996
• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.33

Haploinsufficiency Scores

• pHI: 0.180
• hipred: N
• hipred_score: 0.289
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Oat
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; renal/urinary system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: visual perception;cellular amino acid biosynthetic process;arginine catabolic process to proline via ornithine;arginine catabolic process to glutamate;protein hexamerization;L-proline biosynthetic process
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;mitochondrial matrix
• Molecular function: ornithine-oxo-acid transaminase activity;pyridoxal phosphate binding